1. Field of the Invention
The present invention is related to a composition for regulation of liver X receptor and applications thereof, and the composition comprises fucoxanthin and a metabolite thereof, fucoxanthinol.
2. The Prior Arts
There are various types of photosynthetic pigments in algae, such as chlorophyll, carotene, phycocyanin, phycoerythrin, xanthophyll, etc. Laminaria japonica (seaweed) and Undaria pinnatifida, in particular, are rich in fucoxanthin. Fucoxanthin is an orange-yellow color pigment and unique type of carotenoid found in marine creatures. Previous studies had indicated that, in white adipocytes, fucoxanthin can enhance the activation of Uncoupling protein 1 (UCP1) which breaks down fat tissues and generates brown adipocytes with energy consuming ability. Fucoxanthin can also promote liver to produce docosahexanenoic acid (DHA) and lower the low-density lipoprotein associated with obesity and cardiovascular diseases. Moreover, fucoxanthin is also proven to be able to regulate many kinds of energy-promoting genes in mitochondria.
Liver X receptor (LXR) is a member of the nuclear receptor family and includes two subtypes with similar structure, namely LXRα and LXRβ. The amino acid sequences of the DNA binding domain and ligand binding domain of these two subtypes exhibit 77% consistency. LXRα can be found only in few organ and tissues such as liver, small intestine, adipocytes, and macrophage, whereas LXRβ are distributed throughout almost the entire body. The mechanism of LXR is similar to those of classic nuclear receptors. Upon the ligand binds to and activates LXR, LXR undergoes structural transformation and forms heterodimer with retinolid X receptor (RXR). The LXR-RXR heterodimer then enters the nucleus and binds with DNA, which is the LXR response element (LXRE) of the promoter of the target gene, thus, drives transcription. According to researches, LXRα agonist can reduce the precipitation of cholesterol in blood vessels via activation of LXR. Experimentations had indicated that, if the LXRα gene of mice was knocked out, the mice can remain normal when fed with normal diet; however, when the mice were fed with diet with exceeded cholesterol, fatty liver disease and blood vessel blockage occurred. On the other hand, there were also studies shown that agonist of LXR can inhibit growth of carcinoma cells. Artificial LXR agonist T0901317 (N-(2,2,2-trifluoroethyl)-N-[4-[2,2,2-trifluoro-1-hydroxy-1-(trifluoromethyl)ethyl]phenyl]-benzenesulfonamide) can bind most strongly to LXR; thus, can inhibit the growth of carcinoma cells to the greatest extend. As a result, carcinoma cells with higher LXR expression are more likely to be inhibited by LXR agonist. When LXR were introduced to carcinoma cells with low LXR expression for overexpression, cells not likely to be inhibited by LXR agonist changed into those likely to be inhibited by LXR agonist, indicating that the inhibitory effect is through LXR. Yet, artificial LXR agonist, the abovementioned T0901317 for example, causes side effects such as accumulation of triglyceride in liver when overdose.
The raw materials used in the present invention are fucoxanthin and its metabolite, fucoxanthinol, from those algae can be used for regulating LXR, which can serve as safe and side effect-free compositions of healthy food or pharmaceuticals for improving the symptoms caused by lacking LXR in cells.